Linezolid, a novel oxazolidinone antibiotic: Assessment of monoamine oxidase inhibition using presser response to oral tyramine

The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the presser response to oral tyramine. Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate alternative methods for quantifying the presser effect. Subjects received linezolid (625 mg bid orally) moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a > 30 mmHg increase in systolic blood pressure (SBP) (PD> 30), a positive presser response was defined as a PD> 30 index (pretreatment/treatment ratio of PD> 30) of greater than or equal to 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively Responses returned to baseline within a days of drug discontinuation. The ratio of mean greatest SEP and heart rate at the time of greatest SEP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restrictions. Restrictions to normal dietary intake of tyramine-containing foods are not warranted when taking linezolid. (C) 2001 the American College of Clinical Pharmacology.